Role of Screening Lung Function Tests in a Routine Health Checkup.

Background and objectives The lung function test is a gold standard, guideline-recommended test to detect obstructive airway diseases like asthma and COPD. It is of considerable value in detecting the presence and severity of airflow obstruction in patients with respiratory symptoms. However, the role of spirometry in a routine health checkup is controversial. Spirometry, when used in routine health checkup settings as a case-finding tool for all adults with persistent respiratory symptoms or having a history of exposure to risk factors, is likely to label a relatively large proportion of individuals as diseased with airflow obstruction. Conversely, spirometry is normal in a relatively large percentage of adults who report respiratory symptoms including dyspnea, the respiratory symptom having the greatest impact on quality of life. The objective of this study is to determine the utility of spirometry as a screening test to detect airflow obstruction in otherwise healthy subjects undergoing a routine health checkup. Methods This observational study was conducted with 538 health checkup individuals aged 18 and over. A brief history was taken prior to the test. Lung function tests were performed and interpreted as per the Global Initiative for Chronic Obstructive Lung Disease criteria. The anthropometric and spirometric data obtained were compared to other population-based spirometric studies to compare the prevalence of airflow limitation, the risk factors, and smoking history. Results Of the total 538 subjects incorporated in the study, 305 (57%) were males and 233 (43%) were females aged between 18 to 80 years with a mean age of 45 years. The male-to-female ratio was 1.3:1 with a mean BMI of 25.9. The overall yield from lung function tests in detecting airflow obstruction was 63 subjects (11.7%), of which 36 (11.8%) were males and 27 (11.5%) were females. Seventy-three subjects (13.5%) were classified as having a small airway obstruction, of which 34 were males (46.6%), and 39 were females (53.4%). The distribution of airflow obstruction by age was with eight subjects (5.4%) in the 18-35 group, 21 subjects (7.8%) in the 36-55 group, and 34 (25%) in the elderly (>55) age group. Although overall smoking history showed no significant association with developing airflow obstruction, significant association with smoking was found in the elderly (>55) age group. Interpretation and conclusions The results of the study suggest that lung function tests should be included in routine health checkups in the subset of individuals greater than 35 years of age with or without a history of smoking, in all age groups with a family history of asthma, in individuals with respiratory symptoms and in individuals greater than 55 years of age with a moderate history of smoking.

Temporomandibular Disorders: Implications in Restorative Dentistry and Orthodontics.

Over the past several decades, the science of restorative/reconstructive dentistry and orthodontics has evolved tremendously, following sound principles passed down from robust literature and scientific rationale. These principles have been solid and instrumental in enhancing dentistry, from a single tooth restoration to complex full-mouth rehabilitations. However, it must be noted that some of the principles and philosophies followed over these decades have been questioned based on the advances in science, technology, and evidence-based medicine. The scenario became complex when clinicians were faced with the question of guidance for optimum joint and muscle health as related to restorative dentistry and orthodontics.

Large-scale measurement of aggregate human colocation patterns for epidemiological modeling.

To understand and model public health emergencies, epidemiologists need data that describes how humans are moving and interacting across physical space. Such data has traditionally been difficult for researchers to obtain with the temporal resolution and geographic breadth that is needed to study, for example, a global pandemic. This paper describes Colocation Maps, which are spatial network datasets that have been developed within Meta's Data For Good program. These Maps estimate how often people from different regions are colocated: in particular, for a pair of geographic regions x and y, these Maps estimate the rate at which a randomly chosen person from x and a randomly chosen person from y are simultaneously located in the same place during a randomly chosen minute in a given week. These datasets are well suited to parametrize metapopulation models of disease spread or to measure temporal changes in interactions between people from different regions; indeed, they have already been used for both of these purposes during the COVID-19 pandemic. In this paper, we show how Colocation Maps differ from existing data sources, describe how the datasets are built, provide examples of their use in compartmental modeling, and summarize ideas for further development of these and related datasets. Among the findings of this study, we observe that a pair of regions can exhibit high colocation despite few people moving between those regions. Additionally, for the purposes of clarifying how to interpret and utilize Colocation Maps, we scrutinize the Maps' built-in assumptions about representativeness and contact heterogeneity.

The World's Longest Functioning Implant: A Verified Case Report.

Satisfactory function, esthetics, and phonetics together with long-term stability and minimal complications are all considered as metrics that define a successful outcome. The current case report is documentation of a mandibular subperiosteal implant with a successful follow-up of 56 years. Numerous issues can be credited for the long-term successful outcome including selection of the patient, heedfulness of basic anatomic and physiologic principles, design of the implant and superstructure, surgical execution, application of sound restorative principles, conscientious hygiene, and clockwork recare. The case demonstrates intense cooperation and coordination among the surgeon, restorative dentist, and laboratory technical staff, together with long-lasting patient compliance. Execution of the treatment with a mandibular subperiosteal implant helped this patient overcome the status of a dental cripple. The highlight of the case is that it is the longest success ever documented in the history of any type of implant treatment.

Exploratory analysis of demographic data, tobacco habits, and oral health-related quality of life among complete denture patients.

Aim: The present study assessed the impact of demographics and tobacco habits on oral health related quality of life (OHRQoL) among complete denture patients. Setting and Design: Prospective cohort study design. Materials and Methods: Two hundred and eighty four edentulous patients, aged above 30 years, were chosen as the sample for the study after taking informed consent. Information regarding demographic data and smoking status was obtained from each participant. OHRQoL was evaluated using the Oral Health Impact Profile Edentulousness (OHIP EDENT) quantifying various domains, namely functional limitation, physical pain, psychological discomfort, physical disability, psychological disability, social disability, and handicap. Statistical Analysis Used: Data were analyzed using the Statistical Package for the Social Sciences version 23.0 (IBM; Chicago, Illinois, USA). Mann-Whitney U test was applied to find significant differences in OHRQoL between gender, age, and smoking status. P < 0.05 was considered to be statistically significant. Results: It was seen that complete denture wearers above 65 years had higher OHIP EDENT scores as compared to younger counterparts suggesting the compromised quality of life in the functional domain which was statistically significant. Psychological discomfort was greater in females while physical disability seemed higher in males. Smoking was found to be a factor associated with decreased OHRQoL. Conclusion: Older age groups, female gender, and smoking were factors associated with decreased OHRQoL among complete denture patients.

Survey of Dental Clinicians for Attitude and Use of Torque-Limiting Devices.

PURPOSE: The purpose of this study was to survey practicing clinicians and determine if differences existed concerning their use of torque-limiting devices (TLDs) and screw-tightening protocols, comparing this with existing universal industry standards. MATERIALS AND METHODS: A nine-question survey was administered with 428 dentists providing data for three specific areas: (1) demographic information-TLD ownership, device age, frequency of use, and observations of screw loosening; (2) recognition information-calibration, reading measurements of the TLD, and the meaning of preload; (3) usage information-screw-tightening protocols and effect of speed during actioning of the TLD. Data collection was compared with industry standards for use of hand torque tools including ISO-6789 1,2:2017 and related texts pertaining to screw fastener protocols. RESULTS: The beam-type TLD was the most popular; however, 33% surveyed used it incorrectly. Most TLDs being used were older than 1 year, with only 6% calibrated. Forty-eight percent observed screw loosening less than once per year, while 44% reported three or more occurrences per year. A similar number used the TLD for implant placement and abutment screw tightening. Screw-tightening protocols varied. Preload was not understood by the majority of those surveyed. CONCLUSION: Dentistry does not appear to adhere to the protocols and standards recommended by other industries that also rely on screw-fastening mechanisms and TLDs. Further education and training appears to be warranted in this area of implant dentistry to reduce the risks of screw-associated complications.

Immune Suppression of Glia Maturation Factor Reverses Behavioral Impairment, Attenuates Amyloid Plaque Pathology and Neuroinflammation in an Alzheimer's Disease Mouse Model.

Alzheimer's disease (AD) is an irreversible progressive neurodegenerative disorder recognized by accumulation of amyloid-plaques (APs) and neurofibrillary tangles (NFTs) and eventually loss of memory. Glia maturation factor (GMF), a neuroinflammatory protein first time isolated and cloned in our laboratory plays an important role in the pathogenesis of AD. However, no studies have been reported on whether anti-GMF antibody administration could downregulate neuroinflammation and attenuate amyloid pathology in AD brain. We investigated the potential effect of single dose of (2 mg/kg b.wt/mouse) intravenously (iv) injected with anti-GMF antibodyon cognitive function, neuroprotection, neuroinflammation and Aß load in the brain of 9-month-old 5XFAD mice. Following 4 weeks of anti-GMF antibody delivery in mice, we found reduced expression of GMF, astrocytic glial fibrillary acidic protein (GFAP) and microglial ionizing calcium binding adaptor molecule 1 (Iba1) as well as improvement inneuroinflammatory response via inhibition of pro-inflammatory cytokines (TNF-α, IL-1ß and IL-6) production and amyloid pathology in the cerebral cortex and hippocampal CA1 region of 5XFAD mice. Correspondingly, blockade of GMF function with anti-GMF antibody improved spatial learning, memory, and long-term recognition memory in 5XFAD mice. The present study demonstrates that the immune checkpoint blockade of GMF function with anti-GMF antibody coordinates anti-inflammatory effects to attenuate neurodegeneration in the cortex and hippocampal CA1 region of 5XFAD mouse brain. Further, our data suggest, that pharmacological immune neutralization of GMF is a promising neuroprotective strategy totherapeutically target neuroinflammation and neurodegeneration in AD. Graphical Abstract 5XFAD mice Polyclonal anti-GMF antibody.

Microbial Genetics: Stress Management.

Microbes constitute the very core of our existence. Long believed to be a nuisance and proponents of various disease, latest research point toward their functions in processes that can prove beneficial for human survival and afford long-term protection from disease. The wide range of functions exhibited by a host of microbes implies diversity and heterogeneity at the level of the molecular machinery, thus stressing the need to take a closer look at the molecular underpinnings that dictate distinct outcomes.

Real-Time Noninvasive Bioluminescence, Ultrasound and Photoacoustic Imaging in NFκB-RE-Luc Transgenic Mice Reveal Glia Maturation Factor-Mediated Immediate and Sustained Spatio-Temporal Activation of NFκB Signaling Post-Traumatic Brain Injury in a Gender-Specific Manner.

Neurotrauma especially traumatic brain injury (TBI) is the leading cause of death and disability worldwide. To improve upon the early diagnosis and develop precision-targeted therapies for TBI, it is critical to understand the underlying molecular mechanisms and signaling pathways. The transcription factor, nuclear factor kappa B (NFκB), which is ubiquitously expressed, plays a crucial role in the normal cell survival, proliferation, differentiation, function, as well as in disease states like neuroinflammation and neurodegeneration. Here, we hypothesized that real-time noninvasive bioluminescence molecular imaging allows rapid and precise monitoring of TBI-induced immediate and rapid spatio-temporal activation of NFκB signaling pathway in response to Glia maturation factor (GMF) upregulation which in turn leads to neuroinflammation and neurodegeneration post-TBI. To test and validate our hypothesis and to gain novel mechanistic insights, we subjected NFκB-RE-Luc transgenic male and female mice to TBI and performed real-time noninvasive bioluminescence imaging (BLI) as well as photoacoustic and ultrasound imaging (PAI). Our BLI data revealed that TBI leads to an immediate and sustained activation of NFκB signaling. Further, our BLI data suggest that especially in male NFκB-RE-Luc transgenic mice subjected to TBI, in addition to brain, there is widespread activation of NFκB signaling in multiple organs. However, in the case of the female NFκB-RE-Luc transgenic mice, TBI induces a very specific and localized activation of NFκB signaling in the brain. Further, our microRNA data suggest that TBI induces significant upregulation of mir-9-5p, mir-21a-5p, mir-34a-5p, mir-16-3p, as well as mir-155-5p within 24 h and these microRNAs can be successfully used as TBI-specific biomarkers. To the best of our knowledge, this is one of the first and unique study of its kind to report immediate and sustained activation of NFκB signaling post-TBI in a gender-specific manner by utilizing real-time non-invasive BLI and PAI in NFκB-RE-Luc transgenic mice. Our study will prove immensely beneficial to gain novel mechanistic insights underlying TBI, unravel novel therapeutic targets, as well as enable us to monitor in real-time the response to innovative TBI-specific precision-targeted gene and stem cell-based precision medicine.

Acute Traumatic Brain Injury-Induced Neuroinflammatory Response and Neurovascular Disorders in the Brain.

Acute traumatic brain injury (TBI) leads to neuroinflammation, neurodegeneration, cognitive decline, psychological disorders, increased blood-brain barrier (BBB) permeability, and microvascular damage in the brain. Inflammatory mediators secreted from activated glial cells, neurons, and mast cells are implicated in the pathogenesis of TBI through secondary brain damage. Abnormalities or damage to the neurovascular unit is the indication of secondary injuries in the brain after TBI. However, the precise mechanisms of molecular and ultrastructural neurovascular alterations involved in the pathogenesis of acute TBI are not yet clearly understood. Moreover, currently, there are no precision-targeted effective treatment options to prevent the sequelae of TBI. In this study, mice were subjected to closed head weight-drop-induced acute TBI and evaluated neuroinflammatory and neurovascular alterations in the brain by immunofluorescence staining or quantitation by enzyme-linked immunosorbent assay (ELISA) procedure. Mast cell stabilizer drug cromolyn was administered to inhibit the neuroinflammatory response of TBI. Results indicate decreased level of pericyte marker platelet-derived growth factor receptor-beta (PDGFR-ß) and BBB-associated tight junction proteins junctional adhesion molecule-A (JAM-A) and zonula occludens-1 (ZO-1) in the brains 7 days after weight-drop-induced acute TBI as compared with the brains from sham control mice indicating acute TBI-associated BBB/tight junction protein disruption. Further, the administration of cromolyn drug significantly inhibited acute TBI-associated decrease of PDGFR-ß, JAM-A, and ZO-1 in the brain. These findings suggest that acute TBI causes BBB/tight junction damage and that cromolyn administration could protect this acute TBI-induced brain damage as well as its long-time consequences.

Microbial Genetics: Stress Management.

Microbes constitute the very core of our existence. Long believed to be a nuisance and proponents of various diseases, latest research point toward their functions in processes that can prove beneficial for human survival and afford long-term protection from disease. The wide range of functions exhibited by a host of microbes implies diversity and heterogeneity at the level of the molecular machinery, thus stressing the need to take a closer look at the molecular underpinnings that dictate distinct outcomes.

Neuroprotective effects of flavone luteolin in neuroinflammation and neurotrauma.

Neuroinflammation leads to neurodegeneration, cognitive defects, and neurodegenerative disorders. Neurotrauma/traumatic brain injury (TBI) can cause activation of glial cells, neurons, and neuroimmune cells in the brain to release neuroinflammatory mediators. Neurotrauma leads to immediate primary brain damage (direct damage), neuroinflammatory responses, neuroinflammation, and late secondary brain damage (indirect) through neuroinflammatory mechanism. Secondary brain damage leads to chronic inflammation and the onset and progression of neurodegenerative diseases. Currently, there are no effective and specific therapeutic options to treat these brain damages or neurodegenerative diseases. Flavone luteolin is an important natural polyphenol present in several plants that show anti-inflammatory, antioxidant, anticancer, cytoprotective, and macrophage polarization effects. In this short review article, we have reviewed the neuroprotective effects of luteolin in neurotrauma and neurodegenerative disorders and pathways involved in this mechanism. We have collected data for this study from publications in the PubMed using the keywords luteolin and mast cells, neuroinflammation, neurodegenerative diseases, and TBI. Recent reports suggest that luteolin suppresses systemic and neuroinflammatory responses in Coronavirus disease 2019 (COVID-19). Studies have shown that luteolin exhibits neuroprotective effects through various mechanisms, including suppressing immune cell activation, such as mast cells, and inflammatory mediators released from these cells. In addition, luteolin can suppress neuroinflammatory response, activation of microglia and astrocytes, oxidative stress, neuroinflammation, and the severity of neuroinflammatory diseases such as Alzheimer's disease, Parkinson's disease, multiple sclerosis, and TBI pathogenesis. In conclusion, luteolin can improve cognitive decline and enhance neuroprotection in neurodegenerative diseases, TBI, and stroke.

Senescent cells promote tissue NAD+ decline during ageing via the activation of CD38+ macrophages.

Declining tissue nicotinamide adenine dinucleotide (NAD) levels are linked to ageing and its associated diseases. However, the mechanism for this decline is unclear. Here, we show that pro-inflammatory M1-like macrophages, but not naive or M2 macrophages, accumulate in metabolic tissues, including visceral white adipose tissue and liver, during ageing and acute responses to inflammation. These M1-like macrophages express high levels of the NAD-consuming enzyme CD38 and have enhanced CD38-dependent NADase activity, thereby reducing tissue NAD levels. We also find that senescent cells progressively accumulate in visceral white adipose tissue and liver during ageing and that inflammatory cytokines secreted by senescent cells (the senescence-associated secretory phenotype, SASP) induce macrophages to proliferate and express CD38. These results uncover a new causal link among resident tissue macrophages, cellular senescence and tissue NAD decline during ageing and offer novel therapeutic opportunities to maintain NAD levels during ageing.

Current Trends in Biomarkers for Traumatic Brain Injury.

Neurotrauma, especially Traumatic Brain Injury (TBI) is a major health concern not only for the civilian population but also for the military personnel. Currently there are no precision and regenerative therapies available for the successful treatment of TBI patients. Hence, early detection and treatment options may prevent the severity and untoward harmful effects of TBI. However, currently there are no effective biomarkers available for the rapid and robust diagnosis as well as prognosis of TBI. Several biomarkers in blood, cerebrospinal fluid (CSF), saliva and urine have been explored to assess the onset, progression, severity and prognosis of TBI recently. Present knowledge on the blood biomarkers including cytokines and chemokines and in vivo imaging modalities are useful to some extent to detect and treat TBI patients. Here, we review S100B, Glial Fibrillary Acidic Protein (GFAP), Neuron Specific Enolase (NSE), Myelin Basic Protein (MBP), Ubiquitin C-terminal Hydrolase L1 (UCHL1), tau protein, and alpha spectrin II break down products regarding their usefulness as a set of reliable biomarkers for the robust diagnosis of TBI. We suggest that these biomarkers may prove very useful for the diagnosis and prognosis of TBI.

Glia Maturation Factor (GMF) Regulates Microglial Expression Phenotypes and the Associated Neurological Deficits in a Mouse Model of Traumatic Brain Injury.

Traumatic brain injury (TBI) induces inflammatory responses through microglial activation and polarization towards a more inflammatory state that contributes to the deleterious secondary brain injury. Glia maturation factor (GMF) is a pro-inflammatory protein that is responsible for neuroinflammation following insult to the brain, such as in TBI. We hypothesized that the absence of GMF in GMF-knockout (GMF-KO) mice would regulate microglial activation state and the M1/M2 phenotypes following TBI. We used the weight drop model of TBI in C57BL/6 mice wild-type (WT) and GMF-KO mice. Immunofluorescence staining, Western blot, and ELISA assays were performed to confirm TBI-induced histopathological and neuroinflammatory changes. Behavioral analysis was done to check motor coordination ability and cognitive function. We demonstrated that the deletion of GMF in GMF-KO mice significantly limited lesion volume, attenuated neuronal loss, inhibited gliosis, and activated microglia adopted predominantly anti-inflammatory (M2) phenotypes. Using an ELISA method, we found a gradual decrease in pro-inflammatory cytokines (TNF-α and IL-6) and upregulation of anti-inflammatory cytokines (IL-4 and IL-10) in GMF-KO mice compared with WT mice, thus, promoting the transition of microglia towards a more predominantly anti-inflammatory (M2) phenotype. GMF-KO mice showed significant improvement in motor ability, memory, and cognition. Overall, our results demonstrate that GMF deficiency regulates microglial polarization, which ameliorates neuronal injury and behavioral impairments following TBI in mice and concludes that GMF is a regulator of neuroinflammation and an ideal therapeutic target for the treatment of TBI.